Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, Bangladesh.
Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh.
Virol J. 2023 Jun 19;20(1):127. doi: 10.1186/s12985-023-02030-1.
The next-generation sequencing (NGS) technology facilitates in-depth study of host-pathogen metatranscriptome. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know/understand the dengue virus (DENV) origin and host response with dengue fever.
In this study, blood serum RNA was extracted from 21 dengue patients and 3 healthy individuals. Total transcriptomic data were analyzed for phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools.
The viral genome sequence revealed dengue viral genome size ranges 10647 to 10707 nucleotide. Phylogenetic and phylodynamic analysis showed that the 2021 epidemic isolates were DENV-3 genotype-I and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis showed a total of 2686 genes were DEG in dengue patients compared to control with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = < 0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signaling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was a significant increase of a class of immunoregulatory proteins in dengue patients in compared to the controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signaling pathways were found in dengue patients. These TLR pathways were particularly involved for the activation of innate system coupled with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue.
This is a first report describing DENV complete genomic features and differentially expressed genes in patients in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.
The online version contains supplementary material available at 10.1186/s12985-023-02030-1.
下一代测序(NGS)技术促进了宿主-病原体宏转录组的深入研究。因此,我们通过 NGS 技术结合系统发育和转录组学方法来了解/理解登革热病毒(DENV)的起源和登革热患者的宿主反应。
在这项研究中,从 21 名登革热患者和 3 名健康个体中提取血清 RNA。使用各自的生物信息学工具对全转录组数据进行系统发育、系统发育动力学、差异表达基因(DEG)和基因本体论(GO)分析。
病毒基因组序列显示登革病毒基因组大小范围为 10647 到 10707 个核苷酸。系统发育和系统发育动力学分析表明,2021 年流行株为 DENV-3 基因型-I,与 2019 年流行株相比,形成了一个新的分支。与对照组相比,登革热患者的转录组分析显示共有 2686 个基因的 RNA-seq 数据差异表达的 q 值 < 0.05。DESeq2 图计数功能显示,24 个具有最小差异基因表达 q 值的基因中,有 11 个基因上调,13 个基因下调。GO 分析显示,登革热患者的多细胞生物体、神经系统、化学刺激感觉感知和 G 蛋白偶联受体信号通路过程显著上调(p = < 0.001)。然而,登革热患者的细胞内成分、细胞解剖实体和含有蛋白质的复合物显著下调(p = < 0.001)。重要的是,与对照组相比,登革热患者中有一类免疫调节蛋白显著增加,其免疫系统过程的 GO 增加。此外,还发现登革热患者 Toll 受体(TLR)信号通路的上调。这些 TLR 通路可能参与固有系统与适应性免疫系统的激活,这可能涉及到快速清除感染登革热病毒的细胞。这些差异表达的基因可以进一步研究,以用于登革热的基于靶点的预防干预。
这是首次在孟加拉国报告描述 DENV 完整基因组特征和患者中差异表达的基因。这些基因可能对登革热感染具有诊断和治疗价值。需要持续的基因组监测,以进一步研究与病毒发病机制相关的主要基因型变化。
在线版本包含可在 10.1186/s12985-023-02030-1 获得的补充材料。